What drug is similar to riociguat? Understanding pulmonary hypertension medications

October 9, 2025 •

3 min read

According to a 2023 meta-analysis, switching to riociguat from phosphodiesterase-5 (PDE5) inhibitors can significantly improve hemodynamics and exercise capacity in some pulmonary hypertension patients. While no direct generic equivalent exists, the question of what drug is similar to riociguat involves exploring other medications acting on the same or related pathways to address the condition.

Quick Summary

Riociguat is an sGC stimulator for pulmonary hypertension. Similar treatments include other sGC stimulators, PDE5 inhibitors like sildenafil and tadalafil, and prostacyclin agonists such as selexipag, though they have different mechanisms and specific indications.

Key Points

sGC Stimulator Class: Vericiguat (Verquvo) is the only other FDA-approved soluble guanylate cyclase (sGC) stimulator, though its indication is heart failure, not pulmonary hypertension.
PDE5 Inhibitors: Sildenafil (Revatio) and tadalafil (Adcirca) target the same nitric oxide pathway but work differently by inhibiting an enzyme that breaks down cGMP.
Prostacyclin Agonists: Selexipag (Uptravi) is a prostacyclin receptor agonist that acts on a different pathway to cause vasodilation.
Mechanism Differences: Riociguat both directly stimulates sGC and sensitizes it to NO, while PDE5 inhibitors only block the degradation of cGMP.
Indications Vary: Riociguat is approved for both PAH and CTEPH, while many alternatives like selexipag and PDE5 inhibitors are only approved for PAH.
Switching Strategies: For some patients with intermediate-risk PAH who don't respond well to PDE5 inhibitors, switching to riociguat has shown clinical benefits.
Medical Supervision is Necessary: Selecting the appropriate medication for pulmonary hypertension is complex and requires careful evaluation by a healthcare provider.

Understanding Riociguat's Mechanism of Action

To understand what drug is similar to riociguat, it's crucial to first grasp its unique mechanism. Riociguat (brand name Adempas) is a soluble guanylate cyclase (sGC) stimulator approved for treating both pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Unlike many other pulmonary hypertension drugs, riociguat has a dual mode of action. It works by:

Directly stimulating sGC independently of nitric oxide (NO).
Increasing the sensitivity of sGC to existing NO.

This dual action leads to increased levels of cyclic guanosine monophosphate (cGMP) inside cells, which causes the smooth muscle of blood vessels to relax (vasodilation) and helps reverse the cellular proliferation and fibrosis associated with these diseases.

sGC Stimulators: The Closest Relatives

The most direct comparisons to riociguat come from its own drug class: soluble guanylate cyclase (sGC) stimulators. The other key member of this class is vericiguat.

Vericiguat (Verquvo)

Vericiguat is another sGC stimulator that operates on the same biological pathway as riociguat. However, its approved use is for a different condition: chronic heart failure with reduced ejection fraction. While the mechanism is similar, its application is distinct, and it is not a direct substitute for riociguat in treating pulmonary hypertension.

Other Pulmonary Hypertension Drug Classes

When looking for drugs that are similar in purpose but not necessarily identical in mechanism, several other classes of medication are used to treat pulmonary hypertension.

Phosphodiesterase-5 (PDE5) Inhibitors

PDE5 inhibitors, such as sildenafil (Revatio) and tadalafil (Adcirca), are commonly used in PAH treatment. They target the same nitric oxide (NO) pathway but operate differently. Rather than stimulating sGC, these drugs block the enzyme PDE5, which is responsible for breaking down cGMP. By inhibiting PDE5, they increase the amount of available cGMP, leading to vasodilation. Their efficacy, however, is dependent on the availability of endogenous NO, which is often diminished in patients with PAH. This contrasts with riociguat's NO-independent activation of sGC.

Prostacyclin Pathway Agents

This class of drugs works by mimicking or activating prostacyclin, a substance that causes blood vessel relaxation and inhibits platelet aggregation.

Prostacyclin Analogs: This group includes epoprostenol (Flolan), treprostinil (Remodulin, Tyvaso), and iloprost (Ventavis), which are administered via continuous infusion, inhalation, or oral tablets.
Prostacyclin Receptor Agonists: Selexipag (Uptravi) is a prostacyclin receptor agonist that mimics the effects of prostacyclin and is taken orally. A key difference is that selexipag is not approved for CTEPH, unlike riociguat.

Endothelin Receptor Antagonists (ERAs)

Endothelin is a substance that causes blood vessels to constrict. ERAs, including bosentan (Tracleer), ambrisentan (Letairis), and macitentan (Opsumit), block the receptors for endothelin, thereby causing vasodilation and reducing pulmonary artery pressure.

Comparison of Riociguat and Similar Drugs


Feature	Riociguat (Adempas)	PDE5 Inhibitors (e.g., Sildenafil)	Prostacyclin Agonists (e.g., Selexipag)
Mechanism	sGC stimulator: Direct stimulation and NO sensitization	PDE5 inhibitor: Blocks cGMP degradation	IP receptor agonist: Mimics prostacyclin
Indications	PAH, CTEPH	PAH	PAH
Dosing Frequency	Three times daily	Varies (e.g., sildenafil three times daily)	Twice daily (oral) or IV
Formulation	Oral tablet	Oral tablet, liquid, IV	Oral tablet, IV
Pregnancy Risk	Category X: Contraindicated	Varies	No specific boxed warning like riociguat

Choosing the Right Treatment

For patients with pulmonary hypertension, the choice of medication depends on the specific diagnosis (PAH vs. CTEPH), disease severity, and individual patient factors. For instance, riociguat is currently the only approved pharmacotherapy for inoperable or persistent/recurrent CTEPH. In cases where patients do not respond sufficiently to PDE5 inhibitors, switching to riociguat may be an effective strategy. Conversely, selexipag offers a different mechanism of action via the prostacyclin pathway. The decision is a complex one, requiring careful evaluation by a healthcare provider.

Conclusion

While no single drug is a direct chemical or mechanistic twin for riociguat, several other medications serve a similar purpose by treating pulmonary hypertension. These include other sGC stimulators (though for different conditions), PDE5 inhibitors like sildenafil and tadalafil, prostacyclin pathway agents such as selexipag, and endothelin receptor antagonists. The best alternative or supplemental therapy is highly individualized and must be determined by a qualified medical professional based on the patient's specific diagnosis and clinical needs.

This information is for educational purposes only and is not a substitute for professional medical advice. Always consult with a healthcare provider for diagnosis and treatment.

Frequently Asked Questions

Revatio (sildenafil) is similar in its goal of treating pulmonary hypertension by acting on the nitric oxide pathway, but its mechanism is different. Revatio blocks the enzyme that breaks down cGMP, while riociguat directly stimulates the enzyme that produces cGMP.

Yes, vericiguat (Verquvo) is another sGC stimulator. However, it is approved for treating chronic heart failure with reduced ejection fraction, not pulmonary hypertension, and is therefore not a direct substitute.

Riociguat and Uptravi (selexipag) both treat pulmonary hypertension but via different pathways. Riociguat is an sGC stimulator, while Uptravi is a prostacyclin receptor agonist. Importantly, riociguat is also indicated for CTEPH, whereas Uptravi is not.

Switching from a PDE5 inhibitor to riociguat has been studied in patients who do not respond adequately to PDE5 inhibitors. Any decision to switch medication must be made by a healthcare provider and requires a proper washout period for the PDE5 inhibitor.

The primary difference is their target on the nitric oxide pathway. Riociguat directly stimulates the soluble guanylate cyclase (sGC) enzyme to produce cGMP, while sildenafil inhibits the phosphodiesterase-5 (PDE5) enzyme that breaks cGMP down.

ERAs like bosentan, ambrisentan, and macitentan are another class of pulmonary hypertension drugs that work by blocking the effects of endothelin, a substance that narrows blood vessels. They represent a different therapeutic approach than riociguat.

For pharmacotherapy, riociguat is currently the only approved drug for inoperable CTEPH or persistent/recurrent CTEPH after surgery. Other drugs primarily treat pulmonary arterial hypertension (PAH).